Window Of Vulnerability Research Articles

Emerging Adulthood

The time it takes to grow up has significantly lengthened in the last 20 years and has led to an independent developmental phase of 18–30 years. Research findings show that the five typical characteristics of emerging adulthood are universal in many industrialized countries, including Germany, with far-reaching consequences for mental health. The focus is on a prolonged and qualitatively changed development of identity with corresponding effects on partnership and work. Broad exploration in both areas, reduced commitment and high instability with frequent changes are characteristic. Altered parenting behavior, such as prolonged support, intrusive control, and problems of parents to separate from their children contribute to a prolongation of the transition. Due to the diverse stresses and the strong increase in mental disorders, this age phase represents a second window of vulnerability. The specific characteristics of this age phase require a different therapeutic approach.

Content of cytochrome P-450 in microsomal fractions of the liver of pregnant rats and their embryos

This article presents a comprehensive examination of the impact of the pesticide “dropp” on the lipid peroxidation (LPO) of microsome membranes and the levels of cytochrome P-450 enzyme within microsomal fractions of pregnant rats and their developing embryos. The study delves into the intricate biochemical responses within these biological systems following exposure to the pesticide. The research uncovers a significant intensification of NADP.Nand ascorbate-dependent lipid peroxidation in the liver microsomes of both pregnant rats and their embryos upon exposure to the “dropp” pesticide. This heightened lipid peroxidation is particularly notable on the 3rd day of pregnancy, accompanied by an elevated concentration of malondialdehyde (MDA), a marker of oxidative stress. Moreover, the study reveals a noteworthy impact of “dropp” on the content of cytochrome P-450 enzyme within the microsomal fraction of the liver in pregnant rats. This enzyme, which plays a vital role in various metabolic processes, experiences a reduction in concentration upon pesticide exposure. The effect is most pronounced on the 3rd and 19th days of pregnancy, highlighting specific time windows of vulnerability. Collectively, these findings provide a nuanced understanding of the biochemical repercussions of “dropp” pesticide exposure on the microsomal membranes and enzyme dynamics within pregnant rats and their developing embryos.

Prenatal and postnatal exposure to PM2 .5 and the risk of tic disorders.

Tic disorders are common neurodevelopmental disorders during childhood. Whether prenatal and postnatal exposure to particulate matter with an aerodynamic diameter less than 2.5μm (PM2.5 ) plays a role in the development of tic disorders remains unexplored. To investigate the association of exposure between PM2.5 during the pregnancy and infancy periods and the risk of tic disorders. This birth cohort study recruited singleton live births at term gestations in central Taiwan from the Taiwan Maternal and Child Health Database between 2004 and 2012 and followed up to the end of 2017. New cases of tic disorders were defined using the ICD-9-CM (307.2) and ICD-10-CM (F95), which include all tic spectrum disorders. We assigned daily PM2.5 concentrations derived from a satellite-based model to individuals based on maternal residential addresses at delivery. We fit Cox proportional hazard model and distributed lag non-linear model to estimate the associations between PM2.5 and tic disorders, with hazard ratio (HR) with 95% confidence interval (CI) as the effect measure. Of the 309,376 singleton live births at term gestations, we identified 5902 (1.9%) tic disorder cases. The HR of tic disorders was positively associated with a 10μg/m3 increase in PM2.5 : during pregnancy HR 1.09, 95% CI 1.04, 1.15 and during infancy HR 1.12, 95% CI 1.06, 1.18. The vulnerable time window for infants with increased risk of tic disorders was 6-52 weeks after birth. We observed a nonlinear relationship between PM2.5 and the risk of tic disorders, with exposure to PM2.5 between 16 and 64 μg/m3 being associated with the risk of tic disorders. The association was restricted to Tourette's disorder group. Infant sex did not modify these associations. Infants delivered at term and exposed to PM2.5 are associated with an increased risk of tic disorders (6-52 weeks). Further studies are needed to confirm these associations.

A comprehensive approach to modeling maternal immune activation in rodents.

Prenatal brain development is a highly orchestrated process, making it a very vulnerable window to perturbations. Maternal stress and subsequent inflammation during pregnancy leads to a state referred to as, maternal immune activation (MIA). If persistent, MIA can pose as a significant risk factor for the manifestation of neurodevelopmental disorders (NDDs) such as autism spectrum disorder and schizophrenia. To further elucidate this association between MIA and NDD risk, rodent models have been used extensively across laboratories for many years. However, there are few uniform approaches for rodent MIA models which make not only comparisons between studies difficult, but some established approaches come with limitations that can affect experimental outcomes. Here, we provide researchers with a comprehensive review of common experimental variables and potential limitations that should be considered when designing an MIA study based in a rodent model. Experimental variables discussed include: innate immune stimulation using poly I:C and LPS, environmental gestational stress paradigms, rodent diet composition and sterilization, rodent strain, neonatal handling, and the inclusion of sex-specific MIA offspring analyses. We discuss how some aspects of these variables have potential to make a profound impact on MIA data interpretation and reproducibility.

In silico mechanisms of arsenic trioxide-induced cardiotoxicity.

It has been found that arsenic trioxide (ATO) is effective in treating acute promyelocytic leukemia (APL). However, long QT syndrome was reported in patients receiving therapy using ATO, which even led to sudden cardiac death. The underlying mechanisms of ATO-induced cardiotoxicity have been investigated in some biological experiments, showing that ATO affects human ether-à-go-go-related gene (hERG) channels, coding rapid delayed rectifier potassium current (I Kr ), as well as L-type calcium (I CaL ) channels. Nevertheless, the mechanism by which these channel reconstitutions induced the arrhythmia in ventricular tissue remains unsolved. In this study, a mathematical model was developed to simulate the effect of ATO on ventricular electrical excitation at cellular and tissue levels by considering ATO's effects on I Kr and I CaL . The ATO-dose-dependent pore block model was incorporated into the I Kr model, and the enhanced degree of ATO to I CaL was based on experimental data. Simulation results indicated that ATO extended the action potential duration of three types of ventricular myocytes (VMs), including endocardial cells (ENDO), midmyocardial cells (MCELL), and epicardial cells (EPI), and exacerbated the heterogeneity among them. ATO could also induce alternans in all three kinds of VMs. In a cable model of the intramural ventricular strand, the effects of ATO are reflected in a prolonged QT interval of simulated pseudo-ECG and a wide vulnerable window, thus increasing the possibility of spiral wave formation in ventricular tissue. In addition to showing that ATO prolonged QT, we revealed that the heterogeneity caused by ATO is also an essential hazard factor. Based on this, a pharmacological intervention of ATO toxicity by resveratrol was undertaken. This study provides a further understanding of ATO-induced cardiotoxicity, which may help to improve the treatment for APL patients.

Assessment of Chestnut Gall Toughness: Implications for a Biocontrol Agent.

(1) Torymus sinensis, the biocontrol agent of the Asian chestnut gall wasp Dryocosmus kuriphilus, is univoltine, but in NW Italy a small percentage of individuals exhibits a prolonged diapause, mainly as late instar larva. (2) In 2020, the diapause was investigated to evaluate its trend over the years. Due to the low survival rate of diapausing T. sinensis adults, the seasonal variation in the galls' toughness was evaluated, thus assuming that dry galls over time can negatively affect emergence. The window of vulnerability of the gall wasp galls was also evaluated in controlled conditions. (3) The results showed that the average number of second year T. sinensis emerging per 100 cells was 0.41 ± 0.05, and dead adults accounted for 4.1 ± 0.23 per 100 cells. Gall toughness resulted in lower values for galls collected in May and June, and then gradually increased over time. In general, no difference was detected in the wall toughness of galls formed during the previous year when compared to current-year dry galls. Oviposition was recorded on all the tested galls collected in May and June, and no difference in the number of oviposition events was detected. Conversely, no oviposition was observed in July. Comparing the number of oviposition events by T. sinensis and the gall toughness, a negative correlation was found (R2 = -0.99). (4) The present findings contribute descriptive information on this gall's structural traits, and the influence on gall wasp management is also discussed.

Dynamic, downstream‐propagating thermal vulnerability in a mountain stream network: Implications for biodiversity in the face of climate change

AbstractAs climate change continues to increase air temperature in high‐altitude ecosystems, it has become critical to understand the controls and scales of aquatic habitat vulnerability to warming. Here, we used a nested array of high‐frequency sensors, and advances in time‐series models, to examine spatiotemporal variation in thermal vulnerability in a model Sierra Nevada watershed. Stream thermal sensitivity to atmospheric warming fluctuated strongly over the year and peaked in spring and summer—when hot days threaten invertebrate communities most. The reach scale (~ 50 m) best captured variation in summer thermal regimes. Elevation, discharge, and conductivity were important correlates of summer water temperature across reaches, but upstream water temperature was the paramount driver—supporting that cascading warming occurs downstream in the network. Finally, we used our estimated summer thermal sensitivity and downscaled projections of summer air temperature to forecast end‐of‐the‐century stream warming, when extreme drought years like 2020–2021 become the norm. We found that 25.5% of cold‐water habitat may be lost under high‐emissions scenario representative concentration pathway (RCP) 8.5 (or 7.9% under mitigated RCP 4.5). This estimated reduction suggests that 27.2% of stream macroinvertebrate biodiversity (11.9% under the mitigated scenario) will be stressed or threatened in what was previously cold‐water habitat. Our quantitative approach is transferrable to other watersheds with spatially replicated time series and illustrates the importance of considering variation in the vulnerability of mountain streams to warming over both space and time. This approach may inform watershed conservation efforts by helping identify, and potentially mitigate, sites and time windows of peak vulnerability.

Air pollution exposure and the risk of macrosomia: Identifying specific susceptible months

Birth weight is an important indicator of future growth and development for newborns. Few studies investigated the potential effects of air pollutants on macrosomia and their susceptible windows. We included 38,971 singleton full-term births from Beijing HaiDian Maternal and Child Health Hospital between 2014 and 2018, and assessed the associations of air pollutants exposure during preconception and pregnancy with macrosomia as well as the corresponding susceptible windows. The concentrations of air pollutants (PM2.5, PM10, SO2, NO2, CO and O3) for participants were calculated by the data from the nearest monitoring stations. Distributed lag models (DLM) incorporating logistic regression models were used to estimate the associations between air pollutants exposure during the 3 months before conception and pregnancy period and the risk of macrosomia, identifying susceptible windows of air pollutants. Weighted quantile sum (WQS) regression was applied to estimate the joint effect of air pollutants. A 10 μg/m3 increase in PM2.5 exposure from 3rd to 8th gestational month was positively associated with the risk of macrosomia, with the strongest effect in the 6th month (OR = 1.010, 95 % CI: 1.002–1.019). For a 10 μg/m3 increase in SO2, the windows of significant exposure were from the 1st preconception month to the 3rd gestational month, with the strongest effect in the 2nd month (OR = 1.030, 95 % CI: 1.010–1.049). We also observed the significant positive associations were in the 5th–8th gestational months for PM10, the 8th–9th gestational months for NO2 and the 3rd-7th gestational months for CO respectively. WQS regression also indicated a positive association between co-exposure to air pollutants and macrosomia. Our results suggest air pollution exposure is associated with increased risk of macrosomia. The windows of exposure for susceptibility to the risk of macrosomia vary between air pollutants. The susceptible exposure windows were middle and late pregnancy for PM, CO and NO2, while for SO2, early pregnancy is the window of vulnerability. Our findings provide the evidence that air pollution exposure is an independent risk factor for macrosomia and a basis for targeted environment policy.

Carnosic Acid Mitigates Depression-Like Behavior in Ovariectomized Mice via Activation of Nrf2/HO-1 Pathway

The peri- and post-menopausal periods have been described as the “window of vulnerability” for the development of depressive symptoms that impair women activities and quality of life. The etiopathogenesis of these symptoms is multifactorial and may confer resistance to traditional antidepressants. Attention is now directed toward phytochemicals for their pleiotropic functions and safer profiles. This study investigated the possible perturbation of the nuclear factor erythroid 2–related factor 2 (Nrf2) signaling pathways as an underlying mechanism of post-ovariectomy depression and highlighted the potential benefits of carnosic acid (CA) on the associated behavioral, biochemical, and histopathological alterations. Female Balb/c mice were randomly assigned to be sham-operated or ovariectomized (OVX). After 3 weeks, OVX mice received either a vehicle, CA (20 mg/kg/day), or tin protoporphyrin IX (SnPP-IX; a heme oxygenase-1 (HO-1) inhibitor; 50 μmol/kg/day) for 3 weeks. Our findings revealed that OVX mice had depressive but not anxiety-like behavior. Suppressed Nrf2 and its downstream signaling, and augmented proinflammatory markers were observed in both the hippocampus and prefrontal cortex. CA treatment alleviated depressive behavior, induced the expression of Nrf2, HO-1, thioredoxin-1, and brain-derived neurotrophic factor, and enhanced serotonin levels. CA also suppressed oxidative stress, reduced TNF-α, IL-1β, and iNOS mRNA expression, and ameliorated OVX-induced histopathological changes. SnPP-IX aggravated post-OVX behavioral, neurobiochemical, and histological deteriorations, and reduced CA-protective effects. In conclusion, Nrf2/HO-1 signaling suppression and the associated proinflammatory state are key mechanisms in post-OVX depression. CA exerts multifaceted neuroprotection in OVX mice and represents a promising candidate for clinical evaluation as an antidepressant.

Can the Ebola experience in West Africa help to combat the COVID-19 pandemic? Testing the critical incident management systems model in the COVID-19 context

PurposeThis study explored whether the critical incident management systems (CIMS) model can predict the EMS performance in the COVID-19 context. Past research has established the significance of early detection and response (ER) in the context of Ebola virus disease (EVD), prompting a question of whether the model can also be helpful in the COVID-19 context. Consequently, the authors assessed whether ER influences the impact of communication capacity (CC), reliable information channel (RC) and environment (EN) on COVID-19 EMS performance. Assessing these relationships will advance emerging infectious disease (EID) preparedness.Design/methodology/approachThe authors employed standardized measurement instruments of the CIMS model (CC, ER, RC and EN) to predict the performance of COVID-19 EMS using structural equation modeling (SEM) in a study of 313 participants from frontline responders.FindingsThe results show that the relationship of ER and EN with COVID-19 EMS performance is positive, while that of EN on CC is negative. The relationship between EN and COVID-19 EMS performance was insignificant. Contrary to the hypothesis, CC was negatively significant to COVID-19 EMS performance due to poor communication capacities.Research limitations/implicationsThe authors acknowledge some limitations due to challenges faced in this study. First, Data collection was a significant limitation as these questionnaires were built and distributed in June 2020, but the response time was prolonged due to the recurring nature of the pandemic. The authors had wanted to implore the inputs of all stakeholders, and efforts were made to reach out to various Ministry of Health, the local CDC and related agencies in the region via repeated emails explaining the purpose of the study to no avail. The study finally used the frontline workers as the respondents. The authors used international students from various countries as the representatives to reach out to their countries' frontline workers. Second, since the study was only partially supported using the CIMS model, future studies may combine the CIMS model with other models or theories. Subsequent research reassesses this outcome in other contexts or regions. Consequently, further research can explore how CC can be improved with COVID-19 and another future EID in the region. This may improve the COVID-19 EMS performance, thereby expanding the lesson learned from the pandemic and sustaining public health EID response. Additionally, other authors may combine the CIMS model with other emergency management models or theories to establish a fully supported theoretical model in the context of COVID-19.Practical implicationsThe findings have practical implications for incident managers, local CDCs, governments, international organizations and scholars. The outcome of the study might inform these stakeholders on future direction and contribution to EID preparedness. This study unfolds the impact of lessons learned in the region demonstrated by moderating early detection and responses with other constructs to achieve COVID-19 EMS performance. The findings reveal that countries that experienced the 2013–2016 Ebola outbreak, were not necessarily more prepared for an epidemic or pandemic, judging by the negative moderating impact of early detection and response. However, these experiences provide a foundation for the fight against COVID-19. There is a need for localized plans tailored to each country's situation, resources, culture and lifestyle. The localized plan will be to mitigate and prevent an unsustainable EID management system, post-epidemic fund withdrawals and governance. This plan might be more adaptable and sustainable for the local health system when international interventions are withdrawn after an epidemic. Public health EID plans must be adapted to each country's unique situation to ensure sustainability and constantly improve EID management of epidemics and pandemics in emergency response. The high to moderate importation risk in African countries shows Africa's largest window of vulnerability to be West Africa (Gilbert et al., 2020). Therefore, they should be in the spotlight for heightened assistance towards the preparedness and response for a future pandemic like COVID-19. The West African region has a low capacity to manage the health emergency to match the population capacities. The COVID-19 outbreak in West Africa undoubtedly inflicted many disruptions in most countries' economic, social and environmental circumstances. The region's unique challenges observed in this study with CC and reliable information channels as being negatively significant highlight the poor maintenance culture and weak institutions due to brain drain and inadequate training and monitoring. This outcome practically informs West African stakeholders and governments on aspects to indulge when trying to improve emergency preparedness as the outcomes from other regions might not be applicable.Originality/valueThis study explored the relevance of the CIMS model in the context of the COVID-19 pandemic, revealing different patterns of influence on COVID-19 EMS performance. In contrast to the extant literature on EVD, the authors found the moderating effects of ER in the COVID-19 context. Thus, the authors contribute to the COVID-19 EMS performance domain by developing a context-driven EMS model. The authors discuss the theoretical and practical implications.

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Birth Defects ResearchVolume 114, Issue 18 COVER IMAGEFree Access Cover Image First published: 01 November 2022 https://doi.org/10.1002/bdr2.2107AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Cover legend: Life course considerations of cannabis exposure during vulnerable windows of reproduction and development. (Yassaman Niknam, Francisco Moran, Poorni Iyer, Marlissa Campbell) Volume114, Issue18Special Issue: Emerging understanding of the effects of cannabis use during pregnancyNovember 1, 2022 This article also appears in:Emerging understanding of the effects of cannabis use during pregnancy RelatedInformation

Reward sensitivity and internalizing symptoms during the transition to puberty: An examination of 9-and 10-year-olds in the ABCD Study

Early pubertal timing has been linked to increased risk for internalizing psychopathology in adolescents. Work in older adolescents and adults suggests that heightened reward sensitivity may buffer risk for internalizing symptoms. However, few studies have investigated these associations during the early transition to puberty, a window of vulnerability to mental health risk. In this preregistered study, we investigated the associations among pubertal timing, internalizing symptoms, and reward sensitivity in a large, population-based sample of 11,224 9–10 year-olds from the ABCD Study®. Using split-half analysis, we tested for within-sample replications of hypothesized effects across two age- and sex-matched subsets of the sample. Early pubertal timing was associated with higher internalizing symptoms in female and male participants across samples, with 9–10 year-olds in the mid-pubertal stage at the highest risk for internalizing symptoms. Additionally, early pubertal timing was robustly associated with greater self-reported reward sensitivity in both female and male participants. We observed inconsistent evidence for a moderating role of reward sensitivity across measurement domains (self-report, behavioral, and fMRI data), several of which differed by sex, but none of these interactions replicated across samples. Together, these findings provide unique insights into early indicators of risk for internalizing psychopathology during the transition to puberty in a large, population-based, demographically diverse sample of youth.

Chronicity of repeated blast traumatic brain injury associated increase in oxycodone seeking in rats

Numerous epidemiological studies have found co-morbidity between non-severe traumatic brain injury (TBI) and substance misuse in both civilian and military populations. Preclinical studies have also identified this relationship for some misused substances. We have previously demonstrated that repeated blast traumatic brain injury (rbTBI) increased oxycodone seeking without increasing oxycodone self-administration, suggesting that the neurological sequelae of traumatic brain injury can elevate opioid misuse liability. Here, we determined the chronicity of this effect by testing different durations of time between injury and oxycodone self-administration and durations of abstinence. We found that the subchronic (four weeks), but not the acute (three days) or chronic (four months) duration between injury and oxycodone self-administration was associated with increased drug seeking and re-acquisition of self-administration following a 10-day abstinence. Examination of other abstinence durations (two days, four weeks, or four months) revealed no effect of rbTBI on drug seeking at any of the abstinence durations tested. Together, these data indicate that there is a window of vulnerability after TBI when oxycodone self-administration is associated with elevated drug seeking and relapse-related behaviors.

Seismic responses of infill walls with sliding joints and openings in semi-rigid steel frame

Forming door and window openings in partition infill walls is a frequent activity in engineering practices, while the complexity of the mechanical behavior of such infill systems with openings due to the destructive damage to the infill walls has not been thoroughly considered. To protect the vulnerable door and window openings and mitigate the detrimental multiple diagonal struts effect of infill around the opening, the paper presents two novel precast infill walls with sliding joints and door and window openings for semi-rigid steel frames. The quasi-static cyclic tests are performed on three specimens: a reference bare steel frame and two infilled steel frames with door or window opening. Test results confirm that the developed infill systems effectively prevent potential cracking or deformation of the openings and release the adverse multiple diagonal struts effect of infill with a door or window opening. Because of the working mechanism of the developed infills, the two infilled steel frames behave with similar seismic responses to the bare steel frame, while the novel infills are significantly undamaged and no detectable opening deformation is observed even at the inter-story drift ratio of 3.33%. Furthermore, both experimental and numerical responses of the developed innovative infill systems confirm the effectiveness of the infill systems without any additional fixtures to protect the fragile door and window openings.

Cannabis in Adolescence: Lasting Cognitive Alterations and Underlying Mechanisms.

Cannabis consumption during adolescence is an area of particular concern, owing to changes in the social and political perception of the drug, and presents a scientific, medical, and economic challenge. Major social and economic interests continue to push toward cannabis legalization as well as pharmaceutical development. As a result, shifting perceptions of both legal and illicit cannabis use across the population have changed the collective evaluation of the potential dangers of the product. The wave of cannabis legalization therefore comes with new responsibility to educate the public on potential risks and known dangers associated with both recreational and medical cannabis. Among these is the risk of long-term cognitive and psychological consequences, particularly following early-life initiation of use, compounded by high-potency and/or synthetic cannabis, and heavy/frequent use of the drug. Underlying these cognitive and psychiatric consequences are lasting aberrations in the development of synaptic function, often secondary to epigenetic changes. Additional factors such as genetic risk and environmental influences or nondrug toxic insults during development are also profound contributors to these long-term functional alterations following adolescent cannabis use. Preclinical studies indicate that exposure to cannabinoids during specific windows of vulnerability (e.g., adolescence) impacts neurodevelopmental processes and behavior by durably changing dendritic structure and synaptic functions, including those normally mediated by endogenous cannabinoids and neuronal circuits.

Examining a window of vulnerability for affective symptoms in the mid-luteal phase of the menstrual cycle

Particular phases of the menstrual cycle may exacerbate affective symptoms for females with a diagnosed mental health disorder. However, there are mixed findings regarding whether affective symptoms change across the menstrual cycle in females without a clinical diagnosis. The window of vulnerability model proposes that natural increases in ovarian hormones in the mid-luteal phase of the menstrual cycle lead to systematic changes in brain networks associated with affective processing. Consequently, the model posits that females may experience stress more intensely and remember negative events more readily in the mid-luteal phase, increasing their risk for higher affective symptoms. Using a 35-day longitudinal study design, we tested the window of vulnerability model in a non-clinical sample. We tracked naturally cycling females’ daily stress and three types of affective symptoms: anxious apprehension, anxious arousal, and anhedonic depression. Using multilevel modeling, we simultaneously modeled within- and between-person associations among stress and menstrual phase for each affective symptom. We found increased anhedonic depression in the mid-luteal phase but not anxious apprehension or anxious arousal. Moreover, we detected a positive association between within- and between-person stress and anxious apprehension and anhedonic depression, but not anxious arousal. These associations were not stronger in the mid-luteal phase. Overall, we provide weak evidence for a window of vulnerability for affective symptoms in the mid-luteal phase of the menstrual cycle. Our findings suggest that stress is a better predictor of fluctuations in affective symptoms than the menstrual cycle. Moreover, our findings highlight the importance of measuring multiple negative affective symptoms because they may be differentially related to stress and the menstrual cycle.

The Role of Puberty and Sex on Brain Structure in Adolescents With Anxiety Following Concussion

BackgroundAdolescence represents a window of vulnerability for developing psychological symptoms following concussion, especially in girls. Concussion-related lesions in emotion regulation circuits may help explain these symptoms. However, the contribution of sex and pubertal maturation remains unclear. Using the neurite density index (NDI) in emotion regulation tracts (left/right cingulum bundle [CB], forceps minor [FMIN], and left/right uncinate fasciculus), we sought to elucidate these relationships. MethodsNo adolescent had a history of anxiety and/or depression. The Screen for Child Anxiety Related Emotional Disorders and Children’s Depression Rating Scale were used at scan to assess anxiety and depressive symptoms in 55 concussed adolescents (41.8% girls) and 50 control adolescents with no current/history of concussion (44% girls). We evaluated if a mediation–moderation model including the NDI (mediation) and sex or pubertal status (moderation) could help explain this relationship. ResultsRelative to control adolescents, concussed adolescents showed higher anxiety (p = .003) and lower NDI, with those at more advanced pubertal maturation showing greater abnormalities in 4 clusters: the left CB frontal (p = .002), right CB frontal (p = .011), FMIN left-sided (p = .003), and FMIN right-sided (p = .003). Across all concussed adolescents, lower NDI in the left CB frontal and FMIN left-sided clusters partially mediated the association between concussion and anxiety, with the CB being specific to female adolescents. These effects did not explain depressive symptoms. ConclusionsOur findings indicate that lower NDI in the CB and FMIN may help explain anxiety following concussion and that adolescents at more advanced (vs less advanced) status of pubertal maturation may be more vulnerable to concussion-related injuries, especially in girls.

Modulation of working memory duration by synaptic and astrocytic mechanisms.

Short-term synaptic plasticity and modulations of the presynaptic vesicle release rate are key components of many working memory models. At the same time, an increasing number of studies suggests a potential role of astrocytes in modulating higher cognitive function such as WM through their influence on synaptic transmission. Which influence astrocytic signaling could have on the stability and duration of WM representations, however, is still unclear. Here, we introduce a slow, activity-dependent astrocytic regulation of the presynaptic release probability in a synaptic attractor model of WM. We compare and analyze simulations of a simple WM protocol in firing rate and spiking networks with and without astrocytic regulation, and underpin our observations with analyses of the phase space dynamics in the rate network. We find that the duration and stability of working memory representations are altered by astrocytic signaling and by noise. We show that astrocytic signaling modulates the mean duration of WM representations. Moreover, if the astrocytic regulation is strong, a slow presynaptic timescale introduces a 'window of vulnerability', during which WM representations are easily disruptable by noise before being stabilized. We identify two mechanisms through which noise from different sources in the network can either stabilize or destabilize WM representations. Our findings suggest that (i) astrocytic regulation can act as a crucial determinant for the duration of WM representations in synaptic attractor models of WM, and (ii) that astrocytic signaling could facilitate different mechanisms for volitional top-down control of WM representations and their duration.

Maturation-dependent vulnerability of emotion regulation as a response to COVID-19 related stress in adolescents

BackgroundThe COVID-19 pandemic created unpredictable circumstances resulting in increased psychological strain. Here we investigate pandemic-related alterations in emotion regulation in adolescents assessed before and during the pandemic. We also take biological age into account in the response to the pandemic. MethodsMann-Whitney U tests were conducted to compare baseline data on the Difficulties in Emotion Regulation Scale (DERS) total scores of a pre-pandemic adolescent cohort (n = 241) with those obtained during the second wave of the pandemic (n = 266). We estimated biological age based on an ultrasonic boneage assessment procedure in a subgroup of males, including grammar school and vocational school students in the 9th and 10th grades, and analyzed their data independently. FindingsThere is a gender difference in the timing of vulnerability for pandemic-related stress in grammar school students: females are affected a year earlier than males. Vocational school male students mature faster than grammar school male students, and the timing of emotional vulnerability also precedes that of the grammar school students'. DiscussionWe interpret our findings within a developmental model suggesting that there might be a window of highest vulnerability in adolescent emotion regulation. The timing of the window is determined by both chronological and biological age, and it is different for females and males. Application to practiceDefining the exact temporal windows of vulnerability for different adolescent cohorts allows for the timely integration of preventive actions into adolescent care to protect mental health during future chronic stressful situations.

Windows of Vulnerability: Consequences of Exposure Timing during the Dutch Hunger Winter.

Prior research on early-life exposures to famine has established in utero development as a critical period of vulnerability to malnutrition. Yet, previous research tends to focus narrowly on this stage, at the expense of a more comprehensive examination of childhood. As a result, the literature has yet to compare the severity of the consequences of exposure to malnutrition across developmentally salient periods. Such comparison is crucial not only in the magnitude of effects but also in the nature of outcomes. Using a restricted population registry-linked health survey, this study examines the Dutch Hunger Winter to provide a comprehensive examination of the long-term consequences of in utero, infant, childhood, and adolescent exposure to famine. The results show malnutrition leads to heterogeneous effects depending on when the exposure occurs. In utero exposure to malnutrition leads to deleterious conditions in physical health and lower socioeconomic attainment. For older cohorts, results suggest a resilience to the effects of malnutrition on physical health in late life, but a higher vulnerability to socioeconomic stunting. Furthermore, the results suggest important gender differences in the long-term impact of malnutrition. Males consistently show stronger negative consequences across a wider array of conditions.